A period of dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) (1–3). The pathophysiological rationale for DAPT after DES-PCI is predicated on the need to prevent stent-related thrombotic complications while vascular healing and platform endothelialization are ongoing, a process that seems to last between 1 and 6 months with new-generation DES (1,2,4). Whether to extend DAPT after this mandatory period to provide a broader atherothrombotic risk protection is currently a matter of debate (1). Prolonged DAPT is associated with significant risk reductions in stent- and nonstent-related cardiac ischemic events, counterbalanced by an increased hazard of major bleeding, which is known to be associated with increased morbidity and mortality (1,2,4). The subtle balance between the ongoing risk of ischemia and bleeding requires a careful evaluation of the individual patient’s clinical and anatomic profile to identify those patients who might benefit from prolonged and/or higher-potency platelet inhibition and those who might be exposed to an excessive risk of bleeding (5).

Coronary artery disease (CAD) complexity significantly influences the effectiveness of invasive revascularization strategies and is associated with a higher risk of adverse events, proportional to its severity and burden (5). Patients undergoing PCI with more advanced CAD and challenging subsets of lesions require more complex procedures and remain at increased risk of mid- to long-term adverse ischemic events (5,6). Although initially the U.S. Food and Drug Administration gave on-label indication for DES use in simple, single, de novo coronary lesions in low-risk patients with CAD, many PCIs are currently performed in patients with high-risk clinical and anatomic features. Additionally, several reports linked specific procedural features with a higher risk of short- and long-term coronary thrombosis (7–11). Within this background, patients with advanced CAD undergoing complex revascularization procedures may benefit from more aggressive long-term medical treatments and risk factor control. We therefore hypothesized that compared with a short-term (3 or 6 months) period of DAPT, a longer regimen of DAPT (≥1 year) will reduce the risk of major adverse cardiac events (MACE) to a greater extent after complex percutaneous coronary revascularization.

Methods

Study design

The present study is a post hoc patient-level pooled analysis of randomized controlled trials (RCTs) designed to investigate the efficacy and safety of long-term (≥1 year) versus short-term (3 or 6 months) DAPT in patients undergoing complex or noncomplex PCI. We pooled patient-level data from RCTs comparing short (3 or 6 months) versus long (≥1 year) duration of DAPT. Randomized trials comparing 1 year versus more than 1 year of DAPT were excluded. The study rationale and search strategy were previously reported (4). Briefly, relevant RCTs were searched using MEDLINE, the Cochrane database, the EMBASE database, tctmd, ClinicalTrials, Clinical Trial Results, Cardiosource, and abstracts and presentations from major cardiovascular meetings using the following key words: randomized clinical trial, drug-eluting stent, dual antiplatelet therapy, clopidogrel, aspirin, and thienopyridines. The most updated or most inclusive data for a given study were chosen for abstraction. Internal validity of RCTs was assessed by evaluating concealment of allocation, blind adjudication of events, and inclusion of all randomized patients in the analysis (Online Appendix). Patient-level data were obtained from the principal investigators of all qualifying trials and combined in a single pooled database. In addition to the previously included RCTs (n = 4) (12–15), we included the SECURITY (Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy) (16) and the ITALIC (Is There A LIfe for DES After Discontinuation of Clopidogrel) (17) trials. The study flow diagram and characteristics of the included studies are described in Online Tables 1 and 2 and Online Figure 1. The present review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements (18).

Study objectives and definitions

The objectives of the present study were to: 1) evaluate the effect of procedural complexity on outcomes after contemporary PCI with DES; and 2) investigate the efficacy and safety of long-term (≥1 year) versus short-term (3 or 6 months) DAPT in patients undergoing complex and noncomplex PCI. Complex PCI was defined as a procedure with at least 1 of the following angiographic characteristics: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion as target lesion. Complex PCI was defined on the basis of previously published reports linking features of procedural complexity with ischemic risk and by the clinical judgment of the investigators who conceived this study (Drs. Giustino, Chieffo, and Colombo) (7–11). Short-term DAPT was defined as a randomized DAPT duration ≤6 months (3 or 6 months), whereas long-term DAPT was defined as a randomized DAPT duration ≥12 months.

The primary efficacy endpoint was MACE, defined as the composite of cardiac death, myocardial infarction (MI), or definite or probable stent thrombosis (ST) at median time of follow-up. The primary safety endpoint was major bleeding at median time of follow-up. The endpoint definitions as applied in each trial were incorporated. Bleeding was defined according to the TIMI (Thrombolysis In Myocardial Infarction) criteria in 4 trials (12,14,15,19), the BARC (Bleeding Academic Research Consortium) criteria in 1 trial, and the REPLACE (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events) criteria in 1 trial (13). Secondary endpoints were the rates of all-cause mortality, cardiac mortality, noncardiac mortality, MI, definite or probable ST, coronary thrombotic events (CTEs) (defined as the composite of MI or definite or probable ST), target vessel revascularization, minor bleeding, and any bleeding. In each trial, a blinded clinical events committee adjudicated events (Online Table 2). Endpoint definitions in each included trial are reported in Online Table 3.

Statistical analysis

Individual patient data was pooled in a single dataset and analyzed with a single-stage approach. The intention-to-treat population was used for the analyses, including all patients according to randomized treatment arm assignment (long- vs. short-term DAPT). Categorical variables are reported as counts and percentages and were compared by the Cochrane-Mantel-Haenszel test, using trial identifier as the stratification variable. Continuous variables are reported as mean ± SD and were compared with 2-way analysis of variance, using trial identifier as the stratification variable. A simple Cox regression model was used to generate cumulative hazard function curves at median time of follow-up for descriptive purposes. Incidence rates and incidence rate differences for the main study endpoints (MACE, CTE, and major bleeding) are reported as 100 patient-days of follow-up.

The adjusted effect of “complex PCI” was estimated with multivariable Cox regression modeling, including “complex PCI” as either a categorical or a continuous (per increase in number of complex PCI features) covariate in the Cox model, stratified by trial identifier. Additionally, to evaluate the effect of the individual complex PCI components on ischemic outcomes, each was included as a separate predictor in the multivariable Cox model. Besides complex PCI, the following covariates were used as candidates for the Cox regression multivariable model: age, sex, prior revascularization (PCI or coronary artery bypass graft), prior MI, hypertension, diabetes mellitus, high-risk acute coronary syndrome (ACS) (including non–ST-segment elevation MI or ST-segment elevation myocardial infarction), current smoking, and stent type. The adjusted effect of complex versus noncomplex PCI was also evaluated according to DES generation (early-generation vs. new-generation) for the main ischemic endpoints. Multicollinearity was evaluated by a visual inspection of correlation matrix and estimation of the variance inflation factor, with >10 used as a threshold to define significant multicollinearity. The proportionality assumption for the Cox models was verified using the Schoenfeld residuals method. Effect estimates are reported with adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

The treatment effect of long- versus short-term DAPT according to PCI complexity was estimated with a Cox regression model stratified by trial identifier. Due to observed imbalances in baseline characteristics, to minimize bias, this Cox regression analysis was also adjusted for a propensity score determined using a logistic regression model for treatment with long- versus short-term DAPT. The following variables were considered for the propensity score determination: age, sex, hypertension, dyslipidemia, smoking, diabetes, prior MI, prior revascularization (PCI or coronary artery bypass graft), high-risk ACS, and type of DES implanted. Goodness-of-fit of the propensity score model was evaluated with the Hosmer-Lemeshow test. The consistency of the treatment effect between the complex and noncomplex PCI groups was evaluated through the inclusion of randomized treatment-by-complex PCI interaction terms.

As in all of the included trials randomization was dissociated from actual treatment divergence (i.e., randomization after PCI and DAPT duration divergence at 6 months), implying that endpoint events occurring prior to treatment divergence could not be attributable to differences in DAPT duration, a landmark analysis at the time of treatment divergence in each trial was performed using a per-treatment cohort. To do so, all patients with endpoint events in the first 6 months (for the SECURITY, PRODIGY [Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study], ITALIC, and EXCELLENT [Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting] trials) and in the first 3 months (for the OPTIMIZE [Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice] and RESET [REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation] trials) were excluded, as well as those randomized to short-term DAPT in whom DAPT was prolonged ≥1 month beyond the period scheduled for treatment cessation and those randomized to long-term DAPT who interrupted treatment more than 1 month before the temporal cutoff for treatment divergence versus short-term DAPT.

To evaluate treatment effect consistency within additional clinical subsets of patients, we evaluated the risk of MACE for long- versus short-term DAPT across the complex PCI components and in the following clinical subgroups of interest within the complex and noncomplex PCI subgroups: age >65 years, sex, diabetes, hypertension, high-risk ACS (including non–ST-segment elevation MI or ST-segment elevation MI), prior MI, prior revascularization, and stent type. For stent type, treatment effect consistency was also assessed for CTE, definite or probable ST, and MI.

Multiple intertrial heterogeneity assessments were performed by the Breslow-Day test, the I2 statistic (with values <25%, 25% to 50%, and >50% representing mild, moderate, and severe heterogeneity, respectively), and by measuring the interaction term between trial identifier and randomized treatment within the Cox models for each outcome of interest. Bias assessment was performed according the Cochrane Collaboration tool (20).

Analyses were performed with IBM SPSS Statistics software, version 20.0 (SPSS, IBM, Armonk, New York) and Stata version 12.0 (Stata Corp., College Station, Texas). A 2-sided p value of ≤0.05 was considered statistically significant for all analyses.

Results

Effect of procedural complexity

Of 9,577 patients with available angiographic characteristics, 1,680 (17.5%) underwent complex PCI. Baseline clinical and procedural characteristics according to PCI complexity are reported in Table 1. Patients who underwent complex PCI more commonly had diabetes. Clinical presentation was similar between groups. Randomization assignment to shorter- or longer-term DAPT was well-balanced between the 2 groups. Overall, new-generation DES were used in approximately 86% of patients across all trials. The prevalence of the complex PCI components in the overall population is illustrated in Figure 1, and the overlap between complex PCI components in Online Table 4.

Baseline Characteristics in All Randomized Patients According to PCI Complexity

At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had higher crude rates of MACE (Table 2, Figure 2A) and CTE (Table 2, Figure 2B), MI, definite or probable ST, target vessel revascularization, and mortality (Table 2). By multivariable Cox regression modeling (Table 3), complex PCI remained strongly associated with increased risk of MACE, CTEs, definite or probable ST, and MI with a magnitude that was comparable to that of a history of prior MI or high-risk ACS presentation. Results were overall comparable following inclusion of left ventricular ejection fraction in the multivariable model (Online Table 5). Complex PCI was not associated with an increased risk of major bleeding at adjusted analyses (Figure 2C).

Adjusted risk of major adverse cardiac events (A), coronary thrombotic events (B), definite or probable stent thrombosis (C), and myocardial infarction (D) across high-risk procedural subsets. *Not estimable because the number of events was too low. Incidence rates are expressed as 100 patient-years of follow-up. Abbreviations as in Figure 2.

Long- versus short-term DAPT in patients with or without complex PCI

Baseline characteristics according to procedural complexity and randomized assignment to long- or short-term DAPT are illustrated in Online Table 6. The differential median exposure time to DAPT between the long- and short-term DAPT groups was 9 months. Results for long- versus short-term DAPT in the complex and noncomplex PCI groups are reported in Table 4. The effect of long-term DAPT was heterogeneous per PCI complexity, with a significant benefit in patients who underwent complex PCI (Figure 4A) (adjusted HR: 0.56; 95% CI: 0.35 to 0.89) compared with those who had noncomplex PCI (adjusted HR: 1.01; 95% CI: 0.75 to 1.35; pinteraction = 0.01). Importantly, the benefit on MACE of long-term DAPT was greater as the number of high-risk procedural features increased (Central Illustration). Long-term DAPT was also associated with significantly greater benefit on the risk of CTEs in patients who underwent complex PCI (Figure 4B) (adjusted HR: 0.57; 95% CI: 0.33 to 0.97) compared with noncomplex PCI (adjusted HR: 0.87; 95% CI: 0.61 to 1.25; pinteraction = 0.04). Long-term DAPT was associated with an increased risk of major bleeding, which was uniform in magnitude and direction between patients with and without complex PCI (Figure 4C) (pinteraction = 0.96). Results were consistent at per-treatment landmark analysis (Figure 5, Online Figure 3). The effect of long-term DAPT on the composite and individual ischemic endpoints was uniform between early- and new-generation DES within the complex PCI group (Online Table 7). There was no evidence of intertrial heterogeneity for all of the investigated endpoints (Online Table 8). Bias assessment is reported in Online Table 9.

Per-Treatment Analysis for Long- Versus Short-Term DAPT in Patients With or Without Complex PCI

Cumulative hazard curves for long-term versus short-term DAPT for major adverse cardiac events (A), coronary thrombotic events (B), and major bleeding (C) in patients with or without complex PCI. Incidence rates are expressed as 100 patient-years of follow-up. Abbreviations as in Figures 2 and 4.

Ischemic and Bleeding Outcomes in All Randomized Patients According to PCI Complexity and DAPT Duration

Long- versus short-term DAPT in patients with or without complex PCI across clinical and angiographic subgroups

The effect of long- versus short-term DAPT in patients who underwent complex and noncomplex PCI across clinical subsets is reported in Table 5. The effect of long- versus short-term DAPT was uniform across subsets within both the complex and noncomplex PCI groups (Table 5) and across the high-risk angiographic subsets included in the complex PCI definition (Online Figure 4).

Effect of Long- Versus Short-Term DAPT on Risk of MACE Across Clinical Subsets Within the Complex and Noncomplex PCI Groups

Discussion

The present study of more than 9,000 patients randomized to different durations of DAPT after PCI with mostly new-generation DES introduces procedural complexity as an ischemic risk factor to take into account for clinical decision-making surrounding DAPT duration. The main findings of the present analysis can be summarized as follows:

1. Patients who underwent complex PCI had a higher risk of MACE and CTE at follow-up. This risk was similar in magnitude to that of other well-established clinical risk factors and tended to be greater for progressively higher degrees of procedural complexity. Additionally, the effect of procedural complexity was uniform between DES generations.

2. DAPT for ≥1 year was associated with a significant benefit on the risk of MACE and CTEs compared with 3 or 6 months of DAPT in patients who underwent complex PCI. Importantly, the anti-ischemic benefits of prolonged DAPT were progressively greater as the degree of procedural complexity increased.

3. The benefits of prolonged DAPT appeared to be uniform across complex PCI components, DES generations, and clinical presentation.

4. Long-term DAPT was associated with an increased risk of major bleeding, irrespective of procedural complexity.

Currently, clinical decision-making on upfront DAPT intensity and duration after coronary stenting is predominantly made on the basis of clinical ischemic and bleeding risk factors. However, it remains unclear whether the degree of procedural complexity substantially influences future ischemic risk and identifies patients who may benefit from longer or more intense antithrombotic therapies. In the present study, PCI complexity not only exerted an effect on ischemic risk proportional to the number of high-risk procedural features (degree of procedural complexity), but also had an overall association with MACE that was similar in magnitude to that of other well-established clinical risk factors. The association between procedural complexity and thrombotic risk is multifactorial, and can be both correlative and causative in nature: first, patients who undergo more complex revascularization procedures may have more advanced CAD and a greater prevalence of comorbidities, implying a status of higher risk for atherothrombosis due to the natural progression of atherosclerotic CAD; second, a greater number of stents implanted and stenting of more complex lesions may act as true mediators of the stent-related thrombotic risk, as these factors directly influence the propensity to platelet activation and intracoronary thrombosis (7,21); and third, PCI in the presence of complex CAD may be associated with a greater likelihood of incomplete myocardial revascularization, with subsequent higher risk of recurrent cardiac ischemic events, ventricular dysfunction, and mortality (5).

DAPT has been established as a standard-of-care treatment to prevent stent- and nonstent-related ischemic events after PCI with DES (1–3). The antithrombotic benefits of DAPT extend beyond the stented vascular segment to the whole coronary circulation and possibly the systemic arterial vasculature. However, because of the systemic effect of pharmacological platelet inhibition, this antithrombotic protection is achieved at the expense of an increased risk of bleeding (1–3). The anti-ischemic and prohemorrhagic effects of DAPT are proportional to the potency and duration of platelet inhibition and are both influenced by the underlying individual ischemic and bleeding risk factors (22,23). In the present study, we clarified the comparative effectiveness of 1 year or more versus 3 or 6 months of DAPT after complex percutaneous revascularization. Prolonged DAPT was associated with a greater anti-ischemic benefit in patients who underwent complex PCI, with an increased magnitude of benefit with greater procedural complexity (Central Illustration). The greater benefits with prolonged DAPT in patients with more complex angiographic features can be explained by the following: 1) more and longer stents implanted imply the presence of additional potential sites of delayed metallic platform endothelialization, which may act as a trigger for platelet activation and arterial thrombosis (7,21); 2) stenting of complex lesions (i.e., bifurcations, longer lesions, or chronic total occlusions) may enhance the risk of stent malapposition, incomplete lesion coverage, and delayed endothelialization, which, in turn, all interplay in enhancing the thrombotic propensity within the target vascular segment (6); and 3) as patients who are undergoing more complex revascularization procedures have more advanced CAD and comorbidities, they are more prone to native plaque progression and acute changes with subsequent atherothrombosis. In the Gene Polymorphism, Platelet Reactivity, and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score studies, high on-clopidogrel platelet reactivity on a background of high SYNTAX score was associated with a 5-fold higher risk of MACE compared with patients with high on-clopidogrel platelet reactivity but a low SYNTAX score (24). In line with these proposed pathobiological mechanisms, prolonged and/or more intensified platelet inhibition may protect from all of the previously mentioned factors. Of paramount importance, the effect of long-term DAPT on the primary efficacy endpoint persisted in the per-treatment landmark analysis in which endpoint events were analyzed after treatment divergence. Considering that 1 of the main limitations of the included trials was that patients were randomized before the scheduled period of DAPT cessation, this observation is reassuring regarding the robustness of the main findings.

Ischemic Benefit of Long-Term DAPT According to the Degree of PCI Complexity

DAPT for ≥1 year significantly reduced the risk of major adverse cardiac events after complex PCI compared with 3 or 6 months of DAPT. Complex PCI was defined as the composite of 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The y-axis displays the adjusted hazard ratios for long-term DAPT on risk of major adverse cardiac events. The x-axis displays the number of high-risk procedural features. Incidence rate differences per 100 patient-years of follow-up per number of high-risk procedural features are displayed above the plot. Complex PCI is associated with increased risk of major adverse cardiac events with a magnitude comparable to that of traditional clinical risk factors (i.e., prior myocardial infarction or acute coronary syndrome presentation). The magnitude of the anti-ischemic effect of long-term DAPT trended to be greater for increase in PCI complexity. CI = confidence interval; DAPT = dual antiplatelet therapy; IRD = incidence rate differences; PCI = percutaneous coronary intervention.

The increased risk of major bleeding with prolonged DAPT is consistent with previous published reports and was uniform between PCI complexity groups (1). Given the greater anti-ischemic benefits of prolonged DAPT, alongside a similar bleeding hazard, the current findings support the hypothesis that patients who undergo complex coronary revascularization will benefit from upfront longer (>1 year) DAPT duration. These findings may provide useful information for practicing cardiologists when decisions regarding the optimal upfront duration of “mandatory DAPT” need to be made. Our results must be put into perspective with the recently developed DAPT risk score and Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients (PARIS) risk scores from the DAPT trial and PARIS registry, respectively (22,23). Our findings complement these scores by introducing the concept that in the presence of a low or moderate bleeding risk, angiographic risk factors, in addition to other, well-established ischemic risk factors, must be taken into account when decisions surrounding DAPT duration have to be made. Finally, the prevalence of “complex PCI” in our study was 18.0%. This is most likely an underestimate because of the exclusion criteria of the individual RCTs included in this pooled analysis; it is plausible that the number of patients receiving complex procedures in a real-world practice is substantially higher.

Study limitations

Although our findings rely on individual patient-level data from prospective randomized trials with data monitoring and event adjudication by clinical event committees, several limitations need to be disclosed. First, our results have to be considered hypothesis-generating, as this is a non–pre-specified, post hoc analysis from RCTs that were not designed to test the benefit of long-term DAPT according to procedural complexity. Second, the included trials had significant design limitations, including lack of statistical power to detect differences in hard endpoints, slow enrollment, premature interruption, lower than expected event rates, open-label design, exclusion of high-risk patients (with low prevalence of high-risk ACS presentations), and treatment crossover. Third, procedural complexity definitions included variables available in the pooled dataset; therefore, other markers of anatomic and/or procedural complexity, such as calcified lesions, graft lesions, rotablator use, Medina class, SYNTAX score, and vessel size, were not available. Fourth, although patient-level pooled analyses overcome some of the limitations of study-level meta-analyses, even the present study is subject to the intrinsic limitations of the included trials, such as relatively limited external validity (due to the inclusion/exclusion criteria of each trial), and the heterogeneous study designs. Fifth, the lack of significant differences according to DAPT duration in the noncomplex PCI cohort does not imply the lack of difference or the lack of benefit of prolonged DAPT in this subset of patients (due to the limited power and follow-up of the included studies).

Conclusions

Patients who undergo complex percutaneous coronary revascularization procedures are at a substantially higher risk of ischemic events, in a graded fashion, with increased procedural complexity. In patients who underwent complex PCI, compared with a short period of DAPT (3 or 6 months), long-term DAPT (≥1 year) significantly reduced the risk of cardiac ischemic events with a magnitude that was greater for higher procedural complexity. The results of the present study suggest that, along with other well-established clinical ischemic risk factors, complexity of coronary artery stenting is an important parameter to take into account in tailoring upfront duration of DAPT, and possibly potency, for cardiac ischemic protection.

Perspectives

COMPETENCY IN MEDICAL KNOWLEDGE: Patients undergoing complex PCI are at higher risk of cardiac ischemic events, in a graded fashion with increase in procedural complexity. In patients who undergo complex PCI, compared with a short period of DAPT (3 or 6 months), longer DAPT (≥1 year) significantly reduced the risk of ischemic events. The magnitude of the benefit of prolonged DAPT seems to be greater as the degree of PCI complexity is higher.

Appendix

Appendix

For an expanded Methods section as well as supplemental figures and tables, please see the online version of this article.

Footnotes

Medtronic provided the data for the OPTIMIZE trial. No sponsor of any of the individual trials had any role in the study design, data interpretation, or drafting of the manuscript. Dr. Palmerini has received a speaker fee from Abbott Vascular; and a research grant from Eli Lilly. Dr. Valgimigli has received speaker or consultant fees from Abbott Vascular, AstraZeneca, Alvimedica, Medtronic, Terumo, and The Medicines Company. Dr. Feres has received speaker fees from Biosensors and Eli Lilly; and has been a consultant for Medtronic and Scitech. Dr. Bhatt has served on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors of the Boston VA Research Institute and Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; has served on the data monitoring committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (continuing medical education steering committees); is Deputy Editor of Clinical Cardiology; is vice chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Toolbox

Thank you for your interest in spreading the word about JACC: Journal of the American College of CardiologyNOTE: We request your email address only as a reference for the recipient. We do not save email addresses.

Your Email *

Your Name *

Send To *

Enter multiple addresses on separate lines or separate them with commas.